Apparatus for obtaining cardiovascular information by measuring between two extremities

ABSTRACT

An apparatus for obtaining information on a cardiovascular system based exclusively on measurements between two limbs and effected with a pair of distal electrodes on each limb. The measurement is made by causing an alternating current to flow between one electrode of each limb and measuring the potential difference between the other two electrodes, one also on each limb. This potential difference has a low frequency component which is an electrocardiogram (ECG) and another component having a frequency of the injected alternating current and from which an impedance plethysmogram (IPG) is extracted. The cardiovascular information is determined by measuring the time interval between any predefined characteristic element of the ECG and IPG.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.14/235,588, filed Jan. 28, 2014, which is based upon and claims thebenefit under 35 U.S.C. §371, of PCT International Application No.PCT/ES2012/070574, filed Jul. 26, 2012, and under 35 U.S.C. §119 ofSpanish Application No. P201131331, filed Jul. 29, 2011, the contents ofwhich are incorporated herein by reference.

FIELD OF THE INVENTION

Measuring and control instrumentation. The present invention relates ingeneral to noninvasive physiological parameter measuring and monitoringsystems.

BACKGROUND ART

Obtaining information on cardiovascular parameters is of greatimportance for ascertaining people's state of health. The availabilityof an apparatus which can obtain said information beat by beatcontinuously, simply and comfortably, without requiring the userthemselves or an assistant to have any specific abilities or training,is of great interest. Particularly, when the measurements are not takenin clinical or health care environments it is very desirable for thesubject not to need any aid to be able to take the measurement.

Among the noninvasive measures providing information on thecardiovascular system, the bioelectric signal measurements are some ofthe easiest to obtain, above all if taken with dry electrodes (withoutconducting gel). This practice limits the measuring areas to the limbs(arms and legs) because the mechanical contact with the electrodes maybe made by fixing them or holding them in the hand or resting the handsor feet on them. The application of electrodes to other parts of thebody, the thorax for example, requires them to be held with meansachieving a sufficient pressure to guarantee a good contact, whichinvolves an obvious inconvenience and requires time for placing them.

Two bioelectric signals that provide information on the cardiovascularsystem are the electrocardiogram (or ECG) and the electrical impedancesignals measured in volumes of the body where there is a variationattributable to the blood flow. The measurement of volume changes(plethysmography) based on measuring the electrical impedance is calledimpedance plethysmography (IPG). Plethysmography based on measuring thelight absorbency is called photoplethysmography (PPG).

The ECG and IPG provide information on the cardiovascular system notonly separately but also jointly. To be precise, the time taken by thearterial pulse wave (involving a simultaneous change of volume) to reacha part of the body depends not only on the distance between said partand the heart, but it also depends on the diameter, thickness andstiffness of the arteries, and on the rheological properties of theblood. A time including said information is the one known as PAT (pulsearrival time), which is of great diagnostic interest. See, for example,Eliakim et al, Pulse wave velocity in healthy subjects and in patientswith various disease states, American Heart Journal, vol. 82, no 4, pp448-457, October 1971. Particularly, the PAT measured between the R waveof the ECG and the foot (starting point of the rapid rise associatedwith the ventricular systole) of the photoplethysmography (PPG) in afinger of one hand is frequently used to estimate the systolic pressure,for example, as described by Chen et al., in “Continuous estimation ofsystolic blood pressure using the pulse arrival time and intermittentcalibration”; Medical and Biological Engineering and Computing, vol. 38,pp. 569-574, 2000. Since both the PPG and the IPG measure changes ofvolume, the wave forms of both signals are analogous, and therefore theIPG has been used as an alternative signal to the PPG to measure timeintervals related with the propagation of the pulse wave in thearteries.

In the document by Bang et al. “A pulse transit time measurement methodbased on electrocardiography and bioimpedance” Biomedical Circuits andSystems Conference (BioCAS) 2009, pp. 153-156 the time elapsed betweenthe ECG R wave, obtained with an electrode on each arm, and the IPGpeak, obtained with four electrodes on the forearm, was measured andthis time was compared with the time elapsed between the ECG R wave andthe PPG peak. The correlation between both times was excellent. Althoughthis method proposed by Bang et al. has the advantage of not requiringelectrodes on the thorax, the use of conventional electrodes (withconducting gel) adhered to the arm to obtain the ECG and IPG makes theprocess slow and uncomfortable.

Another document where the measuring of physiological parameters by theECG and IPG without the necessity of locating electrodes on the thoraxis described in U.S. Pat. No. 6,228,033 for Apparatus and methods for anoninvasive measurement of physiological parameters, to Kööbi et al.,2001. In this patent the IPG is preferably obtained by injecting acurrent between both arms and both legs at the same time, and detectingalso at the same time between both arms and both legs. In this regard,see FIG. 1 herein, where the injection electrodes are the pair 31 andthe pair 32, and the detection electrodes are the pair 11 and the pair12. In a preferred embodiment a detection electrode 11 is about 5 cmfrom an adjacent injection electrode 31. With these electrodeconnections, it is stated in said patent that the IPG obtained reflectsabove all the overall impedance changes between arms and legs, whichwill be proportional to the pumping out of blood from the leftventricle. To obtain a distal pulse wave, Kööbi et al. obtain the IPG ina segment of one limb, by using a further two electrodes (21 and 22).They obtain the ECG with the same electrodes (pair 11 and pair 12) withwhich there is detected the potential difference created by the injectedcurrent to measure the impedance without needing thoracic electrodes.The same document describes that the injection of current to obtain theoverall IPG is always at least between one arm and one leg; a possiblearrangement of the electrodes according to this embodiment is shown inFIG. 2 herein where the injection is through the electrode 31 andelectrode 32 and the detection is through the electrode 11 and theelectrode 12. However, according to Kööbi et al, even in this embodimentwherein injection occurs only through one arm and one foot, to obtainthe distal pulse wave by the IPG in a segment of one limb a further twodetection electrodes (21 and 22) disposed along said segment are stillnecessary. It is concluded, therefore, that according to the methoddescribed in U.S. Pat. No. 6,228,033 simultaneously to obtain a distalpulse wave and the ECG, at least six electrodes are required, althoughthere is obtained also another IPG basically reflecting the impedancechanges in the thorax. To obtain the transit time of the pulse wave to adistal segment, they calculate the distance between the peaks of bothimpedance signals obtained, one from the voltage detected between theelectrode 11 and the electrode 12 (FIG. 2) or between the pair ofelectrodes 11 and the pair of electrodes 12 (FIG. 1) and the other fromthe voltage detected between the electrodes 21 and 22.

On the other hand, this Kööbi et al. patent is contemplated for clinicalenvironments and perhaps for this reason they consider the possibilityof using electrodes with gel as an advantage, since they are common inelectrocardiography. In fact, the four electrodes at least necessary forthe limbs (11, 12, 31 and 32 in FIG. 2) could be replaced by dryelectrodes. On the other hand, if the two electrodes (21 and 22 in FIG.2) required for obtaining a local pulse wave by the IPG in a segment ofa limb were dry, they would have to be held in place by a strap or othersimilar means. Furthermore the need always to have a connection with atleast one arm and one leg does not favor the design of a system socompact as may be needing only both hands or both feet.

The use of electrodes on the limbs and on different parts of the thoraxto measure therebetween the overall electrical impedance and theelectrical impedance at different sections of the body, and the changesthereof over time is also described in the document WO 2005/010640“Non-invasive multi-channel monitoring of hemodynamic parameters” toTsoglin and Margolin, 2005. But, to measure the peripheral blood flowthey use, for example, additional electrodes on one finger (pag. 13 andFIGS. 1, 2I, 3A, 3B, 3C, 4C and 5). Furthermore, although some of theelectrodes used for measuring the bioimpedance are also used to obtainthe ECG, they do not do so simultaneously, but the apparatus includes aswitching circuit (member 29 in FIG. 6 of the document) connecting theelectrodes for carrying out one function or the other, but never bothtogether, whereby it is not possible to obtain cardiovascularinformation from the combination of the simultaneous measurements ofboth.

SUMMARY OF THE INVENTION

The method and apparatus proposed in the invention described hereinafterallow the ECG and a distal pulse wave to be obtained using only twopairs of electrodes, dry or otherwise, it being sufficient for one pairto be in contact with each of the two upper limbs or with each of thetwo lower limbs, although also one pair may be disposed on one arm andthe other pair on one leg, either on the same side or on opposite sidesof the body.

The present invention allows information on the cardiovascular system tobe obtained beat by beat and continuously, by measuring only between twolimbs with one pair of distal electrodes on each of them. To this end,an alternating current is injected between both limbs and the potentialdifference is measured between two electrodes, each being adjacent oneof the two injection electrodes.

Referring to FIG. 3, the excitation signal 300 is an alternating currentwhich is caused to flow between an electrode A which is on a distalsegment of one limb and an electrode B which is on a distal segment ofanother limb. A further two electrodes C and D detect the potential inareas respectively close to each of the injection electrodes, and thepotential difference between them is detected by the detection circuit310. The first pair of electrodes 301 is on one limb and the second pair302 is on another limb.

The voltage at the detector circuit 310 inlet has two components: onelow frequency component (less than 40 Hz) which is the electrocardiogram(or ECG), generated by the body itself owing to the electrical activityof the heart, and a component having the frequency of the injectedalternating current and the amplitude of which depends on the electricalimpedance in the conducting volume through which said current flows.Said impedance has a continuous component of great relative amplitude,due to the basal electrical impedance between the limbs being measured,which will remain constant, and a much smaller variable component, dueto the cardiovascular activity. The registration of this variablecomponent of the electrical bioimpedance is the so-called impedanceplethysmogram (IPG). Therefore, the IPG and the ECG may be separated atthe detector circuit 310 outlet and each of these signals can beamplified by means of respective conventional amplifier circuits 320 and330.

In their article “Sources of error in tetrapolar impedance measurementson biomaterials and other ionic conductors” published in the Journal ofPhysics D: Applied Physics, vol. 40, pp. 9-14, 2007, Grimnes andMartinsen warn that it would be erroneous to assume that when measuringwith four electrodes the impedance is determined only by the volumebetween the detection electrodes and show that the volume between theinjection electrodes and the detection electrodes also contributes tothe impedance. Thus, the measured impedance will be the sum of theimpedance of all the segments between the electrodes, each one weighteddepending on the intrinsic electrical properties of each segment and itssection, those of smaller section being the ones that will have agreater contribution to the total impedance measured.

When measuring between the distal segments of two limbs, the conductingvolume between the injection electrodes is constituted by each limb andthe thorax. Owing to its relative transversal dimensions, it is to beexpected that the thoracic impedance is much smaller than that of thelimbs. Effectively, S. Grimnes, in Table 3 of his article “Impedancemeasurement of individual skin surface electrodes” in Medical andBiological Engineering and Computing, vol. 21, pp. 750-755, 1983, showsthat the impedance between the breastbone and the middle of the thigh isone third of the impedance between the breastbone and the center of theupper arm, one seventh of the impedance of one arm and one tenth of theimpedance of a finger. With this data, since in this invention eachelectrode pair is disposed on the distal segments of a limb, it is to beexpected that a major portion of the impedance obtained is due to thelimb tissues, the section of which is much smaller than that of thethorax. Bearing in mind the abundant presence of arteries in the handsand in the feet, said local impedances will change with each beat due tothe arrival of the arterial pressure pulse and the consequent volumechange. Owing to the breathing and to the ejection of blood from theheart on each beat the thoracic impedance will also change, but sinceits section is much larger, the sensitivity of the electrodes to thesechanges at the thorax will be much lower than the sensitivity to thechanges at the limbs themselves due to the arterial pressure wave.

Once the ECG and the IPG have been digitized, the propagation time ofthe pulse wave may be calculated by measuring the interval between the Rwave of the ECG, for example, and a predefined element of the pulsingcomponent of the impedance, such as the onset of its rapid variation,the point of maximum amplitude (peak), an intermediate point betweenboth (for example, the one corresponding to 10% or 50% of the pulseamplitude), the maximum gradient point, or any other convenient element.These times are related to the elasticity of the arteries and thearterial pressure.

The identification and combination of the predefined elements in the ECGand the IPG may be effected by a processor 340 or an expert usingcursors on the display monitor 350 and may be exported from theprocessor 340 as a reporting function 360. The processor may alsocalculate the amplitude of certain predefined points of the IPG, andwith these amplitudes indices and parameters analogous to those definedin the literature for the equivalent points in the arterial pressurewave, and additional parameters which aid better to characterize thepulse wave form may be defined. The diagnostic value of the indices andparameters traditionally defined for the pressure wave in thecardiovascular system is well documented, for example in the book“McDonald's blood flow in arteries” edited by W. W. Nichols and M. F.O'Rourke and published by Hodder Arnold (London), 2005. Particularly,said indices are used to noninvasively assess the stiffness of thearteries. (See for example the publications “Noninvasive assessment ofarterial stiffness and risk of atherosclerotic events” by Oliver andWebb in Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, pp.554-566, 2003, and “Arterial stiffness and cardiovascular events: theFramingham heart study” by Mitchell et al., in Circulation, vol. 121,pp. 505-511, 2010). With the present invention, it is possible tocalculate said indices and parameters in signals obtained by measuringwith only four electrodes between both hands, between both feet, orbetween one hand and one foot, either on the same side of the body or onopposite sides.

Since in this method there is no need to apply electrodes on the bodytrunk or necessarily on segments of the limbs, but the contact with theelectrodes may be made with the hands or feet, there is obtained theadvantage of being able to use dry electrodes. Thus, the contact withthem may be made, for example, with the fingers of the hands or with thesoles of the feet, to mention two cases particularly comfortable for theuser. But the proposed method does not of itself demand that theelectrodes should be dry, but that they may use a conducting gel, forexample on persons where, because some member has been amputated, themost distal end of a limb is a stump. However, if the electrodes arelocated on the body, the variability of their position is much widerthan when the electrodes are on a surface with which a limb has to makecontact, particularly if the contact is made with the fingers. Since theposition of the electrodes affects the IPG wave form, guaranteeing thatthe position of the contacts is always the same is an importantadvantage.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the arrangement of the electrodes described in a preferredembodiment of U.S. Pat. No. 6,228,033, the designation of the electrodesbeing the same as in the original document.

FIG. 2 shows the arrangement of the electrodes in a derivativeembodiment of the preferred embodiment described in U.S. Pat. No.6,228,033, the designation of the electrodes being the same as in theoriginal document.

FIG. 3 is a block diagram of the proposed measuring method.

FIG. 4 shows a preferred embodiment of the method described in thisinvention.

FIG. 5 shows the ECG and IPG obtained with the preferred embodiment ofFIG. 4.

FIG. 6 shoes the evolution of the PAT measured with the proposed method(solid line) and the PAT measured with the conventional method (from theR wave of the ECG to a point of the PPG (photoplethysmogram)) along aperiodic respiration at a rate of six respirations per minute.

DESCRIPTION OF EMBODIMENTS

FIG. 4 shows a preferred embodiment of the measuring method describedand shown with the diagram of FIG. 3. In this preferred embodiment, boththe electrode pair 301 and the electrode pair 302 are two copper sheetsand both pairs are disposed on a common surface which the user holdswith his/her hands, in such a way that the index finger of the righthand 401 is in contact with the electrode A of the pair 301 and themiddle finger of the same hand is in contact with the electrode C of thesame pair 301. At the same time, the index finger of the left hand 402is in contact with the electrode B of the pair 302 and the middle fingerof the same hand is in contact with the electrode D of the same pair302.

An alternating current source generates the excitation signal 300 whichis a sinusoidal current of 10 kHz and 0.5 mA peak, injected between theelectrodes A and B; this second electrode B is connected to the signalearth of the electronic input circuits of the apparatus. The electrode Cand electrode D are each connected to a unit gain amplifier, theensemble of which constitutes the detector 310. The potential differencebetween the outlets of these two amplifiers is measured with twocircuits with a differential input which are connected in parallel, oneto obtain the IPG and the other to obtain the ECG. In this preferredembodiment, the circuit 320 for obtaining the IPG consists of a highpass filter with differential input and output, with cut-off frequenciesof 1 kHz, followed by a six gain instrumentation amplifier, an amplitudedemodulator based on a coherent detector formed by an amplifier, thegain of which is periodically switched between +1 and −1 synchronouslywith the carrier signal, a filter allowing the frequency band of 0.05 Hzto 30 Hz to pass, and a 14,000 gain output amplifier. The circuit 330for obtaining the ECG consists of a filter having differential inlet andoutlet allowing the frequency band of 0.05 Hz to 100 Hz to pass,followed by an instrumentation amplifier of 1000 gain and a low passfilter with a cut-off frequency of 100 Hz. Both the IPG and the ECG aredigitized with a resolution of 16 bits and a sampling frequency of 10kHz.

The specific elements defined for the ECG and the IPG in this preferredembodiment are the R wave of the ECG and the point on the rising flankof the IPG, the amplitude of which is equidistant from the foot and thepeak of the impedance pulse.

Results

FIG. 5 shows the IPG and the ECG obtained with the described preferredembodiment. It may be seen that the peaks of the upper curve (the IPG)appear always with a considerable delay relative to the peaks of thelower curve, which are the R wave of the ECG. If the detected impedancechanges were those produced on the thorax, the IPG peaks would appearshortly after the R wave, since this coincides with the ventricularsystole and the consequent expulsion of blood from the heart. The longdelay between the IPG peak and the ECG R wave confirms the advantage ofthe electrode arrangement proposed in this invention, where theinjection electrodes are at a distal end of each of two limbs and thedetection electrodes are close to the injection electrodes.

To verify that the PAT interval measured between the two predefinedpoints of the ECG and IPG signals, and identified in the preferredembodiment of this invention, are related to the changes in thepropagation in the pulse wave, there has been carried out an experimentconsisting of breathing with an approximately periodic frequency andcomparing the PAT between the ECG and the IPG obtained with the methoddescribed in this invention with the PAT between the same ECG and IPGobtained with a commercial photoplethysmograph disposed on the ringfinger of one hand; to be precise, the PAT was measured between the Rwave and the point on the rising flank of the PPG, the amplitude ofwhich is that of the foot of the PPG plus 10% of the difference betweenthe peak and the foot of the PPG. It is well known that both thepropagation velocity of the pulse wave and the arterial pressure dependon the breathing, since this causes variation in the intrathoracicpressure. FIG. 6 shows that, on breathing at about 0.1 Hz (approximately6 inhalations per minute) the fluctuations in the PAT measured betweenthe ECG and the IPG coincide closely approximately with the fluctuationsof the PAT measured between the ECG and the PPG. The correlationcoefficient between both signals displayed is 0.93.

Having sufficiently described the invention, as well as a preferredembodiment, it should only be added that it is possible to makemodifications in its constitution, materials used and in the form anddimensions of the electrodes, without deviating from the scope of theinvention defined in the following claims.

1. An apparatus for obtaining information on a cardiovascular system,comprising: a) only two pairs of electrodes, each pair on a respectivelimb, one electrode of each pair being a measuring electrode and theother electrode of each pair being a current injector electrode; b) analternative current source to provide an alternating current having afrequency to the current injector electrodes; c) a device for measuringpotential differences in voltage including a detector to separate, fromthe measured potential differences, a first component corresponding toan electrocardiogram, and a second component having the frequency ofsaid alternating current, wherein the second component has an impedanceincluding a continuous component and a variable component, said variablecomponent corresponding to an impedance plethysmogram; d) a separatorfor separating said continuous component from said variable component,e) a digitizer to digitize said first component and said variablecomponent, f) an identifier to identify predefined elements in each ofsaid first component and said variable component, respectively; g) acalculator to calculate a propagation time of a pulse wave by measuringtime intervals between said predefined elements; and h) an estimator toestimate the cardiovascular system information from said measured timeintervals.
 2. The apparatus of claim 1, wherein one of the limbs is afirst hand, the other of the limbs is a second hand, the electrodes ofone pair are located on two points of the first hand, and the electrodesof the other pair are located on two points of the second hand.
 3. Theapparatus of claim 1, wherein one of the limbs is a first foot, theother of the limbs is a second foot, the electrodes of one pair arelocated on two points of the first foot, and the electrodes of the otherpair are located on two points of the second foot.
 4. The apparatus ofclaim 1, wherein one of the limbs is a hand, the other of the limbs is afoot, the electrodes of one pair are located on two points of the hand,and the electrodes of the other pair are located on two points of thefoot.
 5. The apparatus of claim 1, wherein the predefined elements are afirst predefined element in the electrocardiogram and a first predefinedelement in the impedance plethysmogram, wherein the measured timeintervals are between these first predefined elements.
 6. The apparatusof claim 1, wherein the predefined elements are an onset of rapidvariation, a point of maximum amplitude, an intermediate point, or amaximum gradient point.
 7. The apparatus of claim 6, wherein theintermediate point corresponds to 10% or 50% of a pulse amplitude. 8.The apparatus of claim 1, wherein the predefined elements include an Rwave.
 9. The apparatus of claim 1, wherein both of the electrodes of onepair are close together on the limb.
 10. The apparatus of claim 1,wherein the first component frequency is less than 40 Hz.
 11. Anapparatus for obtaining information on a cardiovascular system,consisting of: a) two pairs of electrodes, each pair on a respectivelimb, one electrode of each pair being a measuring electrode and theother electrode of each pair being a current injector electrode; b) adevice to provide an alternating injected current having a frequency tothe current injector electrodes; c) a device for measuring potentialdifferences in voltage including a detector to separate, from themeasured potential differences, a first component having a low frequencyand corresponding to an electrocardiogram, and a second component havingthe frequency of said alternating injected current, wherein the secondcomponent has an impedance including a continuous component and avariable component, said variable component corresponding to animpedance plethysmogram; d) a separator for separating said continuouscomponent from said variable component, e) a digitizer to digitize saidfirst component and said variable component, f) an identifier toidentify predefined elements in each of said first component and saidvariable component, respectively, and g) a calculator to calculate apropagation time of a pulse wave by measuring time intervals betweensaid predefined elements., and h) an estimator to estimate thecardiovascular system information from said measured time intervals. 12.The apparatus of claim 11, wherein one of the limbs is a first hand, theother of the limbs is a second hand, the electrodes of one pair arelocated on two points of the first hand, and the electrodes of the otherpair are located on two points of the second hand.
 13. The apparatus ofclaim 11, wherein one of the limbs is a first foot, the other of thelimbs is a second foot, the electrodes of one pair are located on twopoints of the first foot, and the electrodes of the other pair arelocated on two points of the second foot.
 14. The apparatus of claim 11,wherein one of the limbs is a hand, the other of the limbs is a foot,the electrodes of one pair are located on two points of the hand, andthe electrodes of the other pair are located on two points of the foot.15. The apparatus of claim 11, wherein both of the electrodes of onepair are close together on the limb.
 16. The apparatus of claim 11,wherein the first component frequency is less than 40 Hz.
 17. Anapparatus for obtaining information on a cardiovascular system,comprising: a) only two pairs of electrodes, each pair on a respectivelimb, one electrode of each pair being a measuring electrode and theother electrode of each pair being a current injector electrode; b) analternative current source to provide an alternating current having afrequency to the current injector electrodes; c) a device for measuringpotential differences in voltage including a detector to separate, fromthe measured potential differences, a first component corresponding toan electrocardiogram, and a second component having the frequency ofsaid alternating current, wherein the second component has an impedanceincluding a continuous component and a variable component, said variablecomponent corresponding to an impedance plethysmogram; and a processorconfigured to carry out a process including— separating said continuouscomponent from said variable component, digitizing said first componentand said variable component, identifying predefined elements in each ofsaid first component and said variable component, respectively;calculating a propagation time of a pulse wave by measuring timeintervals between said predefined elements; and estimating thecardiovascular system information from said measured time intervals. 18.The apparatus of claim 17, wherein one of the limbs is a first hand, theother of the limbs is a second hand, the electrodes of one pair arelocated on two points of the first hand, and the electrodes of the otherpair are located on two points of the second hand.
 19. The apparatus ofclaim 17, wherein one of the limbs is a first foot, the other of thelimbs is a second foot, the electrodes of one pair are located on twopoints of the first foot, and the electrodes of the other pair arelocated on two points of the second foot.
 20. The apparatus of claim 17,wherein one of the limbs is a hand, the other of the limbs is a foot,the electrodes of one pair are located on two points of the hand, andthe electrodes of the other pair are located on two points of the foot.21. The apparatus of claim 17, wherein the predefined elements are afirst predefined element in the electrocardiogram and a first predefinedelement in the impedance plethysmog ram, wherein the measured timeintervals are between these first predefined elements.
 22. The apparatusof claim 17, wherein the predefined elements are an onset of rapidvariation, a point of maximum amplitude, an intermediate point, or amaximum gradient point.
 23. The apparatus of claim 22, wherein theintermediate point corresponds to 10% or 50% of a pulse amplitude. 24.The apparatus of claim 17, wherein the predefined elements include an Rwave.
 25. The apparatus of claim 17, wherein both of the electrodes ofone pair are close together on the limb.
 26. The apparatus of claim 17,wherein the first component frequency is less than 40 Hz.
 27. Anapparatus for obtaining information on a cardiovascular system,consisting of: a) two pairs of electrodes, each pair on a respectivelimb, one electrode of each pair being a measuring electrode and theother electrode of each pair being a current injector electrode; b) adevice to provide an alternating injected current having a frequency tothe current injector electrodes; c) a device for measuring potentialdifferences in voltage including a detector to separate, from themeasured potential differences, a first component having a low frequencyand corresponding to an electrocardiogram, and a second component havingthe frequency of said alternating injected current, wherein the secondcomponent has an impedance including a continuous component and avariable component, said variable component corresponding to animpedance plethysmogram; and a processor configured to carry out aprocess including— separating said continuous component from saidvariable component, digitizing said first component and said variablecomponent, identifying predefined elements in each of said firstcomponent and said variable component, respectively, and calculating apropagation time of a pulse wave by measuring time intervals betweensaid predefined elements, and estimating the cardiovascular systeminformation from said measured time intervals.
 28. The apparatus ofclaim 27, wherein one of the limbs is a first hand, the other of thelimbs is a second hand, the electrodes of one pair are located on twopoints of the first hand, and the electrodes of the other pair arelocated on two points of the second hand.
 29. The apparatus of claim 27,wherein one of the limbs is a first foot, the other of the limbs is asecond foot, the electrodes of one pair are located on two points of thefirst foot, and the electrodes of the other pair are located on twopoints of the second foot.
 30. The apparatus of claim 27, wherein one ofthe limbs is a hand, the other of the limbs is a foot, the electrodes ofone pair are located on two points of the hand, and the electrodes ofthe other pair are located on two points of the foot.
 31. The apparatusof claim 27, wherein both of the electrodes of one pair are closetogether on the limb.
 32. The apparatus of claim 27, wherein the firstcomponent frequency is less than 40 Hz.